Non-fucosylated Anti-hTIGIT mAb

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Human TIGIT antibody - Human IgG1fut
Non-fucosylated Anti-hTIGIT mAb

Anti-hTIGIT-hIgG1fut is a recombinant monoclonal antibody (mAb) featuring a variable region that recognizes human TIGIT and a non-fucosylated constant region of the human IgG1 (hIgG1fut) isotype.

TIGIT (T cell immunoglobulin and ITIM domain) is an inhibitory checkpoint that has been implicated in tumor immunosurveillance [1]. TIGIT is specifically expressed on immune cells including, natural killer (NK) cells and a range of T cell subsets. TIGIT binds to CD155 (PVR) and CD112 (PVRL2, nectin-2), which are expressed on antigen-presenting cells (APCs), T cells, and a variety of non-hematopoietic cells including tumor cells. Interestingly, TIGIT competes with CD226 (also known as DNAM-1) and CD96 (also known as Tactile) for the same ligands [1,2]. Upon binding to its ligand, phosphorylation of TIGIT inhibits the NF-κB, P13K, and MAPK pathways, and leads to a strong reduction of NK cytotoxicity as well as inhibition of T cell activation, proliferation, and effector functions [2,3]. 

The blockade of TIGIT is highly favorable in cancer immunotherapy due to a number of reasons including its low expression in peripheral lymphoid organs and high expression in tumor-infiltrating lymphocytes (TILs), the established synergy of TIGIT with other co-inhibitory immune checkpoints, and its ligands being widely expressed on tumor cells [1,2]. The dual blockade of TIGIT and PD-L1 has shown synergistic effects in a murine tumor model, resulting in complete tumor rejection and induced protective memory responses. A similar synergistic effect has been noted with PD-1 and Tim-3 [1,2]. Interestingly, TIGIT’s role in the tumor microenvironment (TME) may also be intertwined with the microbiome. The suppressive function of TIGIT is also exploited by a bacterium commonly found in the TME Fusobacterum nucleatun, to inhibit protective immune responses [4].

Features of Anti-hTIGIT-hIgG1fut:

  • Targets specifically human TIGIT
  • Features the hIgG1fut constant region for enhanced effector function
  • Functionally validated by flow cytometry

Anti-hTIGIT-hIgG1fut is a non-fucosylated antibody, whereby the absence of fucose residues from N-glycans of the IgG-Fc results in an enhancement of antibody-dependent cellular cytotoxicity (ADCC). This increased ADCC is without any detectable change to complement-dependent cytotoxicity (CDC) or antigen-binding capability. Anti-hTIGIT-hIgG1fut was generated by recombinant DNA technology, produced in CHO cells (deficient for fucosylation), and purified by affinity chromatography with protein G.

References:

  1. Solomon, B. L. et al, 2018. TIGIT: a novel immunotherapy target moving from bench to bedside. Cancer Immunol Immunother 67, 1659-1667.
  2. Anderson, A.C. et al. 2016. Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation. Immunity 44, 989-1004.
  3. Joller, N. et al. 2011. Cutting edge: TIGIT has T cell-intrinsic inhibitory functions. J Immunol 186, 1338-1342.
  4. Gur, C. et al. 2015. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42, 344-355.

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